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| Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00001962 |
Purpose
Participants in this study are suffering from rare and serious blood disorders. In aplastic anemia, the bone marrow stops producing red blood cells, platelets, and white blood cells. In pure red cell aplasia, the bone marrow stops producing red cells, and in amegakaryocytic thrombocytopenic purpura, the bone marrow stops producing platelets.
Current treatment approaches for these disorders include bone marrow transplant and/or immunosuppression. However, bone marrow transplant is not always possible, and immunosuppression has serious side effects.
This study will investigate whether daclizumab can be used to treat these disorders. Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells. It has been used successfully in many transplant patients to reduce the rate of organ rejection.
Participants will undergo a complete history and physical examination. A bone marrow aspiration and biopsy will be performed to confirm the type of bone marrow failure. About 5 tablespoons of blood will be drawn for baseline tests and research purposes. Daclizumab will be administered every 2 weeks by vein in a 30-minute infusion. The first dose will be given at NIH and the next four may be given at NIH or by the participant's primary hematologist. The treatment will last 8 weeks. Participants must also see their referring physician or NIH physicians every 2 weeks for blood counts. In the fourth and eighth weeks of the study and at the 3-month follow-up visit, 2 tablespoons of blood will be drawn at NIH. At the 1-month follow-up visit to NIH, 5 tablespoons of blood will be drawn and another bone marrow aspiration and biopsy performed.
Risks from bone marrow aspiration and biopsy and blood draws include discomfort. Daclizumab is usually well-tolerated; however, it may weaken immunity against certain bacteria and viruses.
| Condition | Intervention | Phase |
|---|---|---|
|
Aplastic Anemia Pure Red Cell Aplasia Diamond Blackfan Anemia |
Drug: Daclizumab Drug: Daclizumab (Zenapax) |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | A Pilot Study of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) in Patients With Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia |
| Estimated Enrollment: | 134 |
| Study Start Date: | November 1999 |
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia; single hematopoietic lineage failures such as pure red cell aplasia, Diamond Blackfan Anemia, agranulocytosis, and amegakaryocytic thrombocytopenic purpura; and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG). However, except for severe aplastic anemia, which has been shown to be appropriately treated with either bone marrow transplantation or a combination of ATG and CSA, single agents or regimens have usually not been applied systematically to other immune-mediated hematologic diseases. In an effort to discover other and especially less toxic treatments for immunologically-mediated bone marrow diseases, we seek to apply a new therapy, a humanized anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb ), to a subset of patients with bone marrow failure. Anti-IL-2R mAb acts against activated lymphocytes, thus sharing an important mechanism of action with ATG. However, the mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals (every 2 weeks).
To test the efficacy of anti-IL-2R mAb (daclizumab), we propose to treat two groups of patients: moderate aplastic anemia and single lineage failure states including pure red cell aplasia or Diamond Blackfan anemia; once every other week for a total of 5 doses. Patients relapsing after response to initial treatment may be treated with 2 additional courses of daclizumab.
Eligibility| Ages Eligible for Study: | 2 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Acquired moderate aplastic anemia. Moderate aplastic anemia is defined as aplastic anemia (hypocellular bone marrow) and no evidence for other disease process and depression of at least two out of three blood counts below the normal values:
but not fulfilling the criteria for severe disease defined by depression of two or three of the peripheral counts:
Or
Acquired pure red cell aplasia or Diamond Blackfan anemia requiring RBC transfusions. Pure red cell aplasia is defined by anemia, reticulocytopenia (reticulocyte count less than or equal to 50,000/mm(3) and absent or decreased marrow erythroid precursors.
Diamond Blackfan anemia is defined by anemia, reticulocytopenia (reticulocyte count less than 50,000/mm(3) and absent or decreased marrow erythroid precursors diagnosed at a very early age
Age greater than or equal to 2 years old.
Weight greater than 12 kg.
Patients or their parent(s)/responsible guardian(s) must be able to comprehend and be willing to sign an informed consent.
EXCLUSION CRITERIA:
Current diagnosis or past history of myelodysplastic syndrome or Fanconi's anemia.
Diagnosis of Diamond-Blackfan anemia and availability of a match related transplant donor.
Known allergy to E.coli-derived products.
Persistant B19 parvovirus infection.
Evidence of uncontrolled infection.
Chronic or current clinically significant infection, including HIV positivity or hepatitis B and C virus infection.
Significant other diseases, congestive heart failure (greater than NY Class II), poorly controlled diabetes mellitus, uncontrolled cardiac arrhythmias.
Subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible
A moribund status or concurrent hepatic, renal, cardiac, metabolic disease of such severity that death within 1-4 weeks from initiation of therapy is likely.
Recent major surgery.
Treatment with an investigational agent other than hematopoietic growth factors within 4 weeks of study entry.
Psychiatric, affective, or other disorder that may compromise the ability to give informed consent or to cooperate in a research study.
Pregnancy or lactation.
Contacts and Locations| Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
| Contact: TTY | 1-866-411-1010 |
| United States, Maryland | |
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
More Information
| Responsible Party: | National Institutes of Health ( Elaine M. Sloand, M.D./National Heart, Lung, and Blood Institute ) |
| Study ID Numbers: | 000029, 00-H-0029 |
| Study First Received: | January 18, 2000 |
| Last Updated: | October 30, 2008 |
| ClinicalTrials.gov Identifier: | NCT00001962 |
| Health Authority: | United States: Federal Government |
|
Immunosuppression T-cells Hematopoiesis |
Monoclonal Antibody Therapy Immunosuppressive Therapy Aplastic Anemia |
|
Hematologic Diseases Daclizumab Pure red cell aplasia Anemia Aase syndrome Pancytopenia Antibodies, Monoclonal Red-Cell Aplasia, Pure |
Antibodies Genetic Diseases, Inborn Diamond Blackfan anemia Anemia, Aplastic Anemia, Diamond-Blackfan Bone Marrow Diseases Aplastic anemia Immunoglobulins |
|
Anemia, Hypoplastic, Congenital Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents Pharmacologic Actions |
